Is DDHD2 p.Arg111fs (c.331_344del) pathogenic?

DDHD2 p.Arg111fs (c.331344del) is classified Likely pathogenic in DDHD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-12-20). Very rare (popmax 0.00133%, afr).

How common is DDHD2 p.Arg111fs (c.331_344del) in the general population?

DDHD2 p.Arg111fs (c.331_344del) is very rare (popmax 0.00133%, afr) (gnomAD).

DDHD2 p.Arg111fs

c.331_344del · rs1554511216 · VCV503937

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.6	GERP 1.2, phastCons 1
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,936 alleles

Overall 0.000657% 1/152,202 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DDHD2
Protein: p.Arg111fs
Coding: c.331_344del
MANE Select: NM_015214
dbSNP: rs1554511216
Type: Deletion
Location: chr8:38234501 (GRCh38)
Gene constraint: LOEUF 0.758 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.70
Residue 111: the wwe domain

Full DDHD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DDHD2 p.Lys124fs Pathogenic/Likely pathogenic ★★ same type
DDHD2 p.Glu414fs Pathogenic ★ same type
DDHD2 p.Gly344fs Likely pathogenic ★ same type
DDHD2 p.Ile405_Phe406insTer Likely pathogenic ★ same type
DDHD2 p.Lys152fs Pathogenic ★ same type
DDHD2 p.Phe601fs Pathogenic ★ same type
DDHD2 p.Tyr661fs Likely pathogenic ★ same type
DDHD2 c.221-1_224del Uncertain significance ★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ddhd2-p-arg111fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown